Development of a Smartphone-Based System for Intrinsically Photosensitive Retinal Ganglion Cells Targeted Chromatic Pupillometry.

Chromatic Pupillometry, used to assess Pupil Light Reflex (PLR) to a coloured light stimulus, has regained interest since the discovery of melanopsin in the intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). This technique has shown the potential to be used as a screening tool for neuro-ophthalmological diseases; however, most of the pupillometers available are expensive and not portable, making it harder for them to be used as a widespread screening tool. In this study, we developed a smartphone-based system for chromatic pupillometry that allows targeted stimulation of the ipRGCs. Using a smartphone, this system is portable and accessible and takes advantage of the location of the ipRGCs in the perifovea. The system incorporates a 3D-printed support for the smartphone and an illumination system. Preliminary tests were carried out on a single individual and then validated on eleven healthy individuals with two different LED intensities. The average Post-Illumination Pupil Light Response 6 s after the stimuli offsets (PIPR-6s) showed a difference between the blue and the red stimuli of 9.5% for both intensities, which aligns with the studies using full-field stimulators. The results validated this system for a targeted stimulation of the ipRGCs for chromatic pupillometry, with the potential to be a portable and accessible screening tool for neuro-ophthalmological diseases.

Challenging Obstetrical Management in Generalized Peritonitis during Pregnancy.

Acute abdomen in pregnancy represents a diagnostic and therapeutic challenge, despite the current advances in modern medicine, since the typical symptoms and altered laboratory parameters mimic normal pregnancy. Acute appendicitis is the most common nonobstetric surgical emergency during pregnancy, with an incidence of 1 per 500-2000 pregnancies. Delayed diagnosis and reluctance to operate on a pregnant woman predispose to adverse maternal and fetal outcomes. The elective termination of pregnancy or interventions to prolong it in the presence of appendicitis is controversial. We present a case of a 38-year-old Caucasian woman, G2P0, admitted to the Obstetric Emergency Department at 13 4/7 weeks of gestation with a primary complaint of severe nausea and vomiting associated with progressive diffuse abdominal pain which had started 7 days before. After the difficulty of inherent differential diagnosis, she was diagnosed with generalized peritonitis due to acute perforated appendicitis. Prompt exploratory laparotomy with appendectomy and drainage of multiple abscesses were performed. Conservative obstetrical management was assumed, with subsequent periodic monitoring of the fetal focus. Due to abdominal compartment syndrome, the abdomen was left open for 4 days. After 7 days in the intensive care unit, recovery was favorable, pregnancy remained uneventful, and a healthy full-term baby was born 27 weeks later. This case represents a successful example of how the cooperation of the obstetrics and general surgery teams and the decision of conservative obstetrical management in the surgical environment contributed to optimizing maternal health, achieving the best obstetrical outcome.

MicroRNA-30a-5pme: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples.

BACKGROUND: The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers. METHODS: Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset. MiR-30a-5p expression and promoter methylation were quantitatively assessed by PCR in a tissue set (Cohort #1) and urine sets (Cohorts #2 and 3) from IPOPorto and Homburg University Hospital. Non-parametric tests were used for comparing continuous variables. MiR-30a-5p promoter methylation (miR-30a-5pme) performance as diagnostic (receiver operator characteristics [ROC] - validity estimates) and prognostic [metastasis-free (MFS) and disease-specific survival (DSS)] biomarker was further validated in urine samples from ccRCC patients by Kaplan Meier curves (with log rank) and both univariable and multivariable analysis. RESULTS: Two significant hypermethylated CpG loci in TCGA ccRCC samples, correlating with miR-30a-5p transcriptional downregulation, were disclosed. MiR-30a-5pme in ccRCC tissues was confirmed in an independent patient's cohort of IPOPorto and associated with shorter time to relapse. In urine samples, miR-30a-5pme levels identified cancer both in testing and validation cohorts, with 83% sensitivity/53% specificity and 63% sensitivity/67% specificity, respectively. Moreover, higher miR-30a-5pme levels independently predicted metastatic dissemination and survival. CONCLUSION: To the best of our knowledge, this is the first study validating the diagnostic and prognostic potential of miR-30a-5pme for ccRCC in urine samples, providing new insights for its clinical usefulness as non-invasive cancer biomarker.

Early prenatal diagnosis of parapagus conjoined twins.

Conjoined twinning occurs in 1/100 of monozygotic twins, 1/50,000 gestations and 1/250,000 live births. It is the consequence of a division event at the primitive streak stage of the human embryonic development, about 13-14 days after fertilisation, in monochorionic monoamniotic gestations. A healthy pregnant woman, Gravida 2 Para 1, was admitted into our Fetal Medicine Unit to perform the first trimester ultrasound. A diagnosis of conjoined parapagus twinning based on ultrasound features was made at 11 weeks of gestation, and the couple decided to terminate the pregnancy. The ultrasound showed two independent skulls and hearts, a shared spine below the thoracic level, and a shared stomach. The pathological findings were slightly different, showing two independent stomachs draining into a common duodenum. The karyotype was 46 XY. Early prenatal ultrasound may provide a window to counsel the family and to offer an early termination of pregnancy.

Rapidly growing abdominopelvic mass - to be or not to be, not all we see is what it seems

The finding of a pelvic mass is often a source of great concern to our patients. Establishing the correct diagnosis and accurately staging these tumors is mandatory, but sometimes difficult, as abdominal masses may prove to be benign or malignant and have different etiologies. We describe a patient with a rapidly growing abdominal mass with weight loss and other accompanying symptoms, that together with the exams performed, posed a genuine diagnostic challenge to the team. Only after surgery the authors reached the definitive diagnosis of leiomyoma. Still waters run deep.(AU)

O achado de uma massa pélvica constitui frequentemente uma preocupação para as nossas pacientes. Estabelecer o correto diagnóstico e o estadiamento destes tumores com precisão é mandatório, mas por vezes difícil, uma vez que as massas abdominais podem ser benignas ou malignas e ter diferentes etiologias. Apresentamos um caso de crescimento rápido de um tumor abdominal associado a perda de peso e outros sintomas, que em conjunto com os exames realizados colocaram um desafio à equipe. Somente após a cirurgia os autores confirmaram o diagnóstico definitivo de leiomioma. As aparências iludem. (AU)

Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release.

In the present work composite nanoparticles with a magnetic core and a chitosan-based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion.

Chitosan-based nanoparticles as drug delivery systems for doxorubicin: Optimization and modelling.

In the present work, two drug delivery systems were produced by encapsulating doxorubicin into chitosan and O-HTCC (ammonium-quaternary derivative of chitosan) nanoparticles. The results show that doxorubicin release is independent of the molecular weight and is higher at acidic pH (4.5) than at physiological pH. NPs with an average hydrodynamic diameter bellow 200nm are able to encapsulate up to 70% and 50% of doxorubicin in the case of chitosan and O-HTCC nanoparticles, respectively. O-HTCC nanoparticles led to a higher amount of doxorubicin released than chitosan nanoparticles, for the same experimental conditions, although the release mechanism was not altered. A burst effect occurs within the first hours of release, reaching a plateau after 24h. Fitting mathematical models to the experimental data led to a concordant release mechanism between most samples, indicating an anomalous or mixed release, which is in agreement with the swelling behavior of chitosan described in the literature.